Selective Nitro Reduction of Ester Substituted Nitroarenes by NaBH₄-FeCl₂

Abstract

This work aimed to explore a novel protocol for selective reduction of the nitro group on the aromatic ring while remaining the ester group unaffected. In this study, NaBH₄-FeCl₂ was disclosed as a key reductant in the process. NaBH₄-FeCl₂-mediated reduction showed high chemoselectivity, gave the desired products in magnificent yield (up to 96%), and was applied to synthesize a key intermediate of vilazodone (an antidepressant drug) on a hectogram scale in a total yield of 81% (two steps). The protocol is practical, and capable of synthesis of a range of aromatic amines, especially those with ester substituted in the ring.

Keywords

ester - nitroarene - selectivity reduction - sodium borohydride - vilazodone

Introduction

Amino is a ubiquitous functional group that has been widely used in the synthesis of many natural products, pharmaceuticals, agrochemicals, and biologically active compounds.[1] [2] [3] Currently, nitro reduction is the predominant strategies applied for the synthesis of amino compounds.[3] Traditional methodologies for nitroarene reduction mainly include direct metal reduction such as Béchamp reduction,[4] [5] [6] [7] [8] [9] [10] [11] hydrogenation,[4] [12] [13] [14] [15] [16] [17] [18] [19] and silyl hydride reduction.[4] [20] Under these conditions, most ester groups would not be affected. However, these protocols suffer from drawbacks such as high economic cost, functional group incompatibility, reagent or environmental hazardousness, and high-pressure equipment dependence. Hence, a benign, green, and efficient method for nitro reduction is still required.

Compared with traditional reducing agents, sodium borohydride (NaBH₄) is mild, homogenous, inexpensive and environmental-friendly for applications in a wide range of reduction processes.[21] However, for the reduction of some less-electronphilic functional groups, the reducibility of NaBH₄ needed to be enhanced by combining with transition metal catalysts.[22] [23] [24] [25] [26] [27] [28] [29] [30] Indeed, NaBH₄ combined transition metal such as Fe,[31] [32] [33] Co,[34] [35] Ni[36] [37] and Cu[38] [39] are available for reducing nitroaromatics to the corresponding aromatic amines, nevertheless, these metal catalysts are associated with one or more problems such as necessity of using metal nanoparticles and was not commercially available, no assess the substrate scope, and poor selectivity, as it did in the case of the process development of vilazodone, of which the key intermediate ethyl 5-nitrobenzofuran-2-carboxylate (1a) is envisioned to be reduced by NaBH₄ during our project development_.

Although in some transition-metal catalyzed protocols, ester groups were reported compatible,[40] [41] [42] [43] [44] [45] the selectivity of nitro group over ester group can still be improved. To verify method applicability in our project, ester substituted nitroarene 1a was subjected to the aforementioned NaBH₄-involved approaches ([Scheme 1]).[45] [46] Disappointingly, 1a was reduced to quite a small amount of the desired aniline compound 1b, yet, (5-nitrobenzofuran-2-yl)methanol (1c), the corresponding primary alcohol with intact nitro group, was the major product. Furthermore, the control experiment (with only NaBH₄) confirmed that only 1c was generated when no other additives were present. Thus, it is still desirable to develop a new methodology for the highly-selective reduction of ester substituted nitroarenes not only in this situation.

Scheme 1 Comparison of NaBH₄-involved approaches of selective nitro reduction.

As mentioned before, we hypothesize that the selectivity could be improved by adding transition metal salts, because NaBH₄ can reduce transition metal salts to zero valence, and the zero valence metals can selectively reduce nitro to amino under special conditions. In addition, the previously reported[47] procedure utilizing CuSO₄ in solvent with NaBH₄ afforded conversion of 1a to the desired product 1b with very low impurity levels, and a large number of 1c was obtained. However, these results also suggest that ester reduction could be inhibited by some salts. Inspired by the previous results, we wonder whether other metal salts could realize the selective reduction of ester substituted aromatic nitro compounds with high conversion.

Results and Discussion

The screening of reduction conditions was conducted in [Table 1]. We began our exploration with 1a as the model substrate. Initially, the reaction was performed in the presence of 1.0 equiv. of MX_n and 2.5 equiv. of NaBH₄ under nitrogen atmosphere in THF at 28°C. The process proceeded slowly to furnish the desired product 1b only in 10.9% conversion when CuSO₄ was used, but 9.41% of 1c was formed ([Table 1], entry 1). In addition, the large amount of 1c was obtained when AlCl₃ or LiCl was used, and the conversions up to 36.1% and 20.2%, respectively ([Table 1], entries 2, 3). Surprisedly, when 1.0 equiv. of FeCl₃ was used, only a small amount of 1c was observed ([Table 1], entry 4, 0.5%). This finding indicated that the reduction of ester group might be suppressed by some metal salts or the reaction proceeded differently. Then, several kinds of ferrous salts were evaluated. Fortunately, we found that FeCl₂ was suitable for this reaction, achieving at high 1b conversion (up to 92.8%), and only 0.1% of 1c was detected, while the others gave poor conversion of 1b (less than 30%, [Table 1], entries 5–8). Subsequently, we attempted to lower the equiv. of NaBH₄ but found that the conversion decreased seriously when the NaBH₄ loading was cut down from 2.5 equiv. to 1.5 or 1.1 equiv. ([Table 1], entries 9–11). Furthermore, testing various amounts of FeCl₂ revealed that 1.0 equiv of FeCl₂ was the best, and the decrease in equiv. of FeCl₂ caused an obvious increase in the content of 1c ([Table 1], entries 12–14). The solvent had a great impact on this reaction. It was found that aprotic solvents contribute to the high conversion, however, in a polar protic solvent (EtOH), poor conversion was provided ([Table 1], entries 6, 15–16). Thus, THF was selected as the optimized solvent for further studies. Finally, we assess the effect of reaction temperature on the conversion. When we lower the reaction temperature, the conversion of 1b was decreases while the content of 1c was increased ([Table 1], entry 17). As such, we tried to improve the reaction rate by raising the temperature from 28 to 40°C. Unexpectedly, the conversion was still low ([Table 1], entry 18). Above all, 2.5 equiv. of NaBH₄, 1.0 equiv. of FeCl₂, THF as the solvent, and reaction temperature at 28°C were set as the optimal reaction conditions.

Table 1 Optimization of the reaction conditions[a]

Entry	MXn (equiv.)	NaBH4 (equiv.)	Solvent	Conv. (%)[b]
				1b	1c
1	CuSO4 (1.0)	2.5	THF	10.9	9.41
2	AlCl3 (1.0)	2.5	THF	31.1	36.1
3	LiCl (1.0)	2.5	THF	2.6	20.2
4	FeCl3 • 6H2O (1.0)	2.5	THF	3.6	0.5
5	FeSO4 • 7H2O (1.0)	2.5	THF	24.0	14.2
6	FeCl2 (1.0)	2.5	THF	92.8 (91.3[ c ])	0.1
7	FeBr2 (1.0)	2.5	THF	trace	1.5
8	FeC2O4 • 2H2O (1.0)	2.5	THF	12.6	36.7
9	FeCl2 (1.0)	2.0	THF	81.9	0.6
10	FeCl2 (1.0)	1.5	THF	60.0	0.3
11	FeCl2 (1.0)	1.1	THF	17.2	0.1
12	FeCl2 (0.8)	2.5	THF	85.5	0.4
13	FeCl2 (0.5)	2.5	THF	71.4	1.2
14	FeCl2 (0.2)	2.5	THF	36.3	10.3
15	FeCl2 (1.0)	2.5	MeCN	77.7	0.2
16	FeCl2 (1.0)	2.5	EtOH	16.5	2.0
17[ d ]	FeCl2 (1.0)	2.5	THF	22.6	1.0
18[ e ]	FeCl2 (1.0)	2.5	THF	33.6	0.5

^a Reaction conditions: 3.8 mmol of 1a, respective mmol of MX_n and NaBH₄ were added into 10 mL of solvent, and the mixture was stirred under nitrogen atmosphere at 25–28 oC for 12 hours.

^b Conversion was determined by HPLC.

^c Yield of isolated product after flash column chromatography on silica gel.

^d Reaction temperature is 15°C.

^e Reaction temperature is 40°C.

To assess the substrate scope, a full set of ester group substituted aromatic nitro compounds were reduced under the optimized conditions. Examination of the results listed in [Table 2] shows that the reaction proceeded well in most cases. For a better understanding, the substrates were divided into different groups depending on the relative position of the nitro and ester groups on the phenyl ring. In group 1, the ester group was located in a meta-position of the nitro group in substrates 2a-2d ([Table 2], entries 1–4), giving 3a-3d in excellent yields (91–96%). In group 2, a series of para-ester nitroarene derivatives were investigated. At first, methyl 4-nitrobenzoate (2e) showed good conversion and obtained the desired product in 93% yield. And the substrates containing an electron-donating group (2f) or an electron-withdrawing group (2 g, 2h) also gave desired products in high yield (92–95%). Generally, unlike meta- or para-ester substituted nitro compounds, the ortho-effect of ester and nitro group in 2i-2k (group 3; [Table 2], entries 9–11) made the selective nitro-reduction more challenging. To our delight, satisfying results were also observed. In contrast, ortho-disubstituted substrate 2j showed an obvious decrease of yield (83%) even under optimized conditions, which was probably due to the steric effect. Meanwhile, we also examined aliphatic ester substrate ([Table 2], entry 12) and acquired the corresponding aniline (3i) in 85% yield.

Table 2 Substrate scopea

^a Reaction conditions: 3.8 mmol of 2, 3.8 mmol of FeCl₂, and 9.5 mmol of NaBH₄ were added into 10 mL of THF, and the mixture was stirred under a nitrogen atmosphere at 25–28°C for 12 hours.

^b Yield of isolated product after flash column chromatography on silica gel.

Heterocycles are prevalent in many pharmacologically important core structures. Selectivity of the nitro group over the ester group in pyridine systems, which were common in pharmaceutical molecules, was also demonstrated by the reduction of 2m and 2n, which proceeded smoothly to provide 3m and 3n in 89% and 92% yield, respectively. To further expand the substrate scope, the substrates bearing nitro and acid groups such as 2-nitrobenzoic acid and 5-fluoro-2-nitrobenzoic acid were also investigated, disappointingly, no more than 10% conversions were detected. This result maybe due to that NaBH₄ was a high energy material that easy decomposed by reacting with carboxy group on the substrates.

Other types of nitro compounds (2o-2q) were also tested under optimized conditions ([Table 2], entries 15–17). Excellent halide compatibility was observed from the above results, and interestingly, cyano group was also observed relatively stable under the same conditions ([Table 2], entry 15). Pleasingly, 4,6-dichloro-5-nitro-2-(propylthio)pyrimidine (2p) and 2-bromo-6-nitrobenzo[d] thiazole (2q) could be reduced with good results (93% and 94% yield, respectively). The corresponding products are important skeletons present in bioactive compounds, such as ticagrelor,[48] and some potential anti-hepatitis C or anti-Alzheimer's disease drugs.[49] [50] [51] [52]

The synthetic utility of this methodology was confirmed in the synthesis of vilazodone. As shown in [Scheme 2], under the optimized conditions, a hectogram scale of 1a was selectivly reduced to give 1b, which was extracted with ethyl acetate, concentrated, and used to produce 1d directly (81% yield, two steps).[53] 1d is the key intermediate for the construction of vilazodone, and proceed to synthsize the target product according to a reported study.[54]

Scheme 2 Synthesis of vilazodone. The starting material 1a was used at 100 g-scale. 1d was obtained from 1b according to Jayaraman et al's method,[53] and then participated the process for producing vilazodone according to a reported study.[54]

Conclusion

In summary, it has been demonstrated that the introduction of FeCl₂ into the NaBH₄ reduction system brings significant benefits for selective nitro reduction. Through this protocol, a range of multi-substituted aromatic amino compounds could be synthesized with excellent yield. Especially, utilization of this method enabled an efficient synthesis of the ester substituted amino compounds. In addition, NaBH₄-FeCl₂-promoted nitro reduction provided a useful synthetic strategy for the synthesis of a key intermediate of the antidepressant drug vilazodone. Further applications of this protocol are currently being explored and will be disclosed in due course.

Experimental section

General Procedure for the Synthesis of 1b, 3a-3q

To a stirred solution of 1a (3.8 mmol) in THF (10 mL) was added FeCl₂ (3.8 mmol) at r.t., then the NaBH₄ (9.5 mmol) was added under nitrogen atmosphere, the resulting solution was stirred for 12 hours at 25–28°C. Water (20 mL) was added to the reaction mixture. The mixture was extracted with CH₂Cl₂ (20mL × 3). The combined extracts were washed with water (20 mL) and concentrated under vacuum. The residue was purified by flash column chromatography on silica gel using ethyl acetate/n-hexane mixture to afford 1b.

Ethyl 5-aminobenzofuran-2-carboxylate (1b): Yellow solid. 91% yield. mp 58–60°C. ESI-HRMS (m/z): calcd. for [M + H]⁺ 206.0812, found 206.0810. ¹H NMR (400 MHz, DMSO) δ 7.51 (s, 1H), 7.38 (d, J = 9.4 Hz, 1H), 6.82 (d, J = 6.9 Hz, 2H), 5.22 (s, 2H), 4.32 (dd, J = 14.1, 7.0 Hz, 2H), 1.32 (t, J = 7.1 Hz, 3H). ¹³C NMR (101 MHz, DMSO-d₆ ) δ 158.82, 148.66, 145.09, 144.77, 127.34, 117.25, 113.65, 111.98, 104.41, 60.86, 14.12.

Full experimental detail for the synthesis of 3a-3q, and the ¹H and ¹³C NMR spectra can be found in Supporting Information of this article's webpage.

Conflict of Interest

All authors declare no conflict of interest.

Acknowledgment

We gratefully thank Lei Zhao (HEC Pharm Co., Inc.) for HPLC assistance.

• Reference

• 1 Downing RS, Kunkeler PJ, van Bekkum H. Catalytic syntheses of aromatic amines. Catal Today 1997; 37 (02) 121-136
• 2 Nandi D, Siwal S, Choudhary M, Mallick K. Carbon nitride supported palladium nanoparticles: An active system for the reduction of aromatic nitro-compounds. Appl Catal A Gen 2016; 523: 31-38
• 3 Lauwiner M, Rys P, Wissmann J. Reduction of aromatic nitro compounds with hydrazine hydrate in the presence of an iron oxide hydroxide catalyst. I. The reduction of monosubstituted nitrobenzenes with hydrazine hydrate in the presence of ferrihydrite. Appl Catal A Gen 1998; 172 (01) 141-148
• 4 Kadam HK, Tilve SG. Advancement in methodologies for reduction of nitroarenes. RSC Advances 2015; 5: 83391-83407
• 5 Nakano S, Inoue N, Hamada Y, Nemoto T. Pd-catalyzed cascade cyclization by intramolecular Heck insertion of an allene-allylic amination sequence: application to the synthesis of 3,4-fused tricyclic indoles. Org Lett 2015; 17 (11) 2622-2625
• 6 Kakuta H, Azumaya I, Masu H. et al. Cyclic-tri(N-methyl-meta-benzamide)s: substituent effects on the bowl-shaped conformation in the crystal and solution states. Tetrahedron 2010; 66 (42) 8254-8260
• 7 Haydon DJ, Bennett JM, Brown D. et al. Creating an antibacterial with in vivo efficacy: synthesis and characterization of potent inhibitors of the bacterial cell division protein FtsZ with improved pharmaceutical properties. J Med Chem 2010; 53 (10) 3927-3936
• 8 Takagi K, Sugimoto S, Yamakado R, Nobuke K. Self-assembly of oligothiophene chromophores by m-calix[3]amide scaffold. J Org Chem 2011; 76 (08) 2471-2478
• 9 Kwak SH, Shin S, Lee JH. et al. Synthesis and structure-activity relationships of quinolinone and quinoline-based P2 × 7 receptor antagonists and their anti-sphere formation activities in glioblastoma cells. Eur J Med Chem 2018; 151: 462-481
• 10 Guo C, Huang K, Wang B, Xie L, Xu X. Palladium-catalyzed annulation reactions of methyl o-halobenzoates with azabicyclic alkenes: a general protocol for the construction of benzo[c]phenanthridine derivatives. RSC Advances 2013; 3: 17271-17280
• 11 Ren Y, Wei H, Yin G, Zhang L, Wang A, Zhang T. Oxygen surface groups of activated carbon steer the chemoselective hydrogenation of substituted nitroarenes over nickel nanoparticles. Chem Commun (Camb) 2017; 53 (12) 1969-1972
• 12 Xu S, Xi X, Shi J, Cao S. A homogeneous catalyst made of poly(4-vinylpyridine-co-N-vinylpyrrolidone)-Pd(0) complex for hydrogenation of aromatic nitro compounds. J Mol Catal Chem 2000; 160: 287-292
• 13 Vanier GS. Simple and Efficient Microwave-Assisted Hydrogenation Reactions at Moderate Temperature and Pressure. Synlett 2007; [phone]
• 14 Tu W, Liu H, Tang Y. The metal complex effect on the selective hydrogenation of m- and p-chloronitrobenzene over PVP-stabilized platinum colloidal catalysts. J Mol Catal Chem 2000; 159: 115-120
• 15 Khilnani VL, Chandalia SB. Selective Hydrogenation. I. para-Chloronitrobenzene to para-Chloroaniline Platinum on Carbon As Catalyst. Org Process Res Dev 2001; 5 (03) 257-262
• 16 Chandrasekhar S, Prakash SJ, Rao CL. Poly(ethylene glycol) (400) as superior solvent medium against ionic liquids for catalytic hydrogenations with PtO2. J Org Chem 2006; 71 (05) 2196-2199
• 17 Jiang C, Shang Z, Liang X. Chemoselective Transfer Hydrogenation of Nitroarenes Catalyzed by Highly Dispersed, Supported Nickel Nanoparticles. ACS Catal 2015; 5 (08) 4814-4818
• 18 Cui X, Zhou X, Dong Z. Ultrathin γ-Fe₂O₃ nanosheets as a highly efficient catalyst for the chemoselective hydrogenation of nitroaromatic compounds. Catal Commun 2018; 107: 57-61
• 19 Zhao Z, Yang H, Li Y, Guo X. Cobalt-modified molybdenum carbide as an efficient catalyst for chemoselective reduction of aromatic nitro compounds. Green Chem 2014; 16: 1274-1281
• 20 Orlandi M, Tosi F, Bonsignore M, Benaglia M. Metal-Free Reduction of Aromatic and Aliphatic Nitro Compounds to Amines: A HSiCl3-Mediated Reaction of Wide General Applicability. Org Lett 2015; 17 (16) 3941-3943
• 21 Nawar N. Iridium carbonyl cluster complexes with bidentate phosphine ligands; the X-ray crystal structure of [Ir₄(CO)₈(dppa)₂]·3(THF). J Organomet Chem 2000; 609: 137-143
• 22 Ranu BC, Samanta S. Reduction of activated conjugated alkenes by the InCl3–NaBH4 reagent system. Tetrahedron 2003; 59 (40) 7901-7906
• 23 Poonam KP, Chauhan SM. Efficient cobalt(II) phthalocyanine-catalyzed reduction of flavones with sodium borohydride. Chem Commun (Camb) 2009; 42 (42) 6397-6399
• 24 Aramini A, Brinchi L, Germani R, Savelli G. Reductions of α,β-Unsaturated Ketones by NaBH₄ or NaBH₄ + CoCl₂: Selectivity Control by Water or by Aqueous Micellar Solutions. Eur J Org Chem 2000; 2000 (09) 1793-1797
• 25 Lundevall FJ, Elumalai V, Drageset A, Totland C, Bjørsvik HRA. Co₂B Mediated NaBH₄ Reduction Protocol Applicable to a Selection of Functional Groups in Organic Synthesis. Eur J Org Chem 2018; 2018 (26) 3416-3425
• 26 Yakabe S, Hirano M, Morimoto T. Hydrogenation of alkenes with sodium borohydride and moist alumina catalyzed by nickel chloride. Tetrahedron Lett 2000; 41 (35) 6795-6798
• 27 Yakabe S, Hirano M, Morimoto T. One-Pot Reduction of Sulfoxides with NaBH₄·CoCl₂•6H₂O Catalyst, and Moist Alumina. Synth Commun 2011; 41 (15) 2251-2255
• 28 Snelling R, Saavedra JZ, Bayrasy P, Abdollahian Y, Singaram B. Binary reducing agents containing dichloroindium hydride for the selective, partial, or tandem reductions of bifunctional compounds consisting of halo-nitriles, halo-esters and halo-carboxylic acids. Org Chem Front 2015; 2: 133-140
• 29 Saavedra JZ, Resendez A, Rovira A, Eagon S, Haddenham D, Singaram B. Reaction of InCl3 with various reducing agents: InCl3-NaBH4-mediated reduction of aromatic and aliphatic nitriles to primary amines. J Org Chem 2012; 77 (01) 221-228
• 30 Formenti D, Ferretti F, Scharnagl FK, Beller M. Reduction of Nitro Compounds Using 3d-Non-Noble Metal Catalysts. Chem Rev 2019; 119 (04) 2611-2680
• 31 Bae S, Gim S, Kim H, Hanna K. Effect of NaBH4 on Properties of Nanoscale Zero-Valent Oron and its Catalytic Activity for Reduction of p-Nitrophenol. Appl Catal B 2016; 182: 541-549
• 32 Zhang X, Chen L, Yun J, Wang X, Kong J. Constructing Magnetic Si-C-Fe Hybrid Microspheres for Room Temperature Nitroarenes Reduction. J Mater Chem A Mater Energy Sustain 2017; 5: 10986-10997
• 33 He S, Niu H, Zeng T, Wang S, Cai Y. A Facile and Efficient Method for Continuous Reduction of Nitroaromatic Compounds Through the Cyclic Transformation Between Fe(II)-complexes and Nano Zero-valent Iron. ChemistrySelect 2016; 1: 2821-2825
• 34 Mandlimath TR, Gopal B. Catalytic Activity of First Row Transition Metal Oxides in the Conversion of p-Nitrophenol to pAminophenol. J Mol Catal Chem 2011; 350: 9-15
• 35 Chen H, Yang M, Tao S, Chen G. Oxygen Vacancy Enhanced Catalytic Activity of Reduced Co3O4 towards p-Nitrophenol Reduction. Appl Catal B 2017; 209: 648-656
• 36 Rahman A, Jonnalagadda SB. Swift and Selective Reduction of Nitroaromatics to Aromatic Amines with Ni−Boride−Silica Catalysts System at Low Temperature. Catal Lett 2008; 123: 264-268
• 37 Kalbasi RJ, Nourbakhsh AA, Babaknezhad F. Synthesis and characterization of Ni nanoparticles-polyvinylamine/SBA-15 catalyst for simple reduction of aromatic nitro compounds. Catal Commun 2011; 12: 955-960
• 38 Hervés P, Pérez-Lorenzo M, Liz-Marzán LM, Dzubiella J, Lu Y, Ballauff M. Catalysis by metallic nanoparticles in aqueous solution: model reactions. Chem Soc Rev 2012; 41 (17) 5577-5587
• 39 Rashid MH, Raula M, Mandal TK. Polymer Assisted Synthesis of Chain-Like Cobalt-Nickel Alloy Nanostructures: Magnetically Recoverable and Reusable Catalysts with high Activities. J Mater Chem 2011; 21: 4904-4917
• 40 Kadam HK, Tilve SG. Copper(II) bromide as a procatalyst for in situ preparation of active Cu nanoparticles for reduction of nitroarenes. RSC Advances 2012; 2: 6057-6060
• 41 Layek K, Kantam ML, Shirai M, Nishio-Hamane D, Sasaki T, Maheswaran H. Gold nanoparticles stabilized on nanocrystalline magnesium oxide as an active catalyst for reduction of nitroarenes in aqueous medium at room temperature. Green Chem 2012; 14: 3164-3174
• 42 Verma PK, Bala M, Thakur K, Sharma U, Kumar N, Singh B. Iron and Palladium(II) Phthalocyanines as Recyclable Catalysts for Reduction of Nitroarenes. Catal Lett 2014; 144 (07) 1258-1267
• 43 Vernekar AA, Patil S, Bhat C, Tilve SG. Magnetically recoverable catalytic Co–Co₂B nanocomposites for the chemoselective reduction of aromatic nitro compounds. RSC Advances 2013; 3: 13243-13250
• 44 Feng YS, Ma JJ, Kang YM, Xu HJ. PdCu nanoparticles supported on graphene: an efficient and recyclable catalyst for reduction of nitroarenes. Tetrahedron 2014; 70 (36) 6100-6105
• 45 Yoo SE, Lee SH. Reduction of Organic Compounds with Sodium Borohydride-Copper(II) Sulfate System. Synlett 1990; 1990 (07) 419-420
• 46 Gohain S, Prajapati D, Sandhu JS. A New and Efficient Method for the Selective Reduction of Nitroarenes: Use of Ammonium Sulphate-Sodium Borohydride. Chem Lett 1995; 24: 725-726
• 47 Sathiyamoorthi S, Almansour AI, Raju SK, Natarajan A, Kumar RR. Imidazolium ylide mediated tandem Knoevenagel–Michael–O-cyclization sequence for the synthesis of multi-substituted 4,5-dihydrofurans. Synth Commun 2021; 51 (02) 234-244
• 48 Voslar M, Strelec I, Dammer O. et al. A production method and a new crystalline form of an intermediate of synthesis of ticagrelor. WO Patent 2015/067230 A1.. May, 2015
• 49 Bort G, Sylla-Iyarreta Veitía M, Ferroud C. Straightforward synthesis of PET tracer precursors used for the early diagnosis of Alzheimers disease through Suzuki–Miyaura cross-coupling reactions. Tetrahedron 2013; 69 (35) 7345-7353
• 50 Buckman B, Nicholas JB, Serebryany V, Seiwert SD. Novel inhibitors of hepatitis C virus replication. WO Patent 2012/087976 A2.. June, 2012
• 51 Gravenfors Y, Jonasson C, Malmstroem J. et al. Novel heteroaryl substituted benzothiazoles. WO Patent 2007/086800.. August, 2007
• 52 Goya-Jorge E, Abdmouleh F, Carpio LE, Giner RM, Sylla-Iyarreta Veitía M. Discovery of 2-aryl and 2-pyridinylbenzothiazoles endowed with antimicrobial and aryl hydrocarbon receptor agonistic activities. Eur J Pharm Sci 2020; 151: 105386
• 53 Jayaraman VR, Rathod D, Vohra I. et al. Process for the preparation of vilazodone hydrochloride and its amorphous form. WO Patent 2013153492 A2.. October, 2013
• 54 Hu B, Song Q, Xu Y. Scale-Up Synthesis of Antidepressant Drug Vilazodone. Org Process Res Dev 2012; 16 (09) 1552-1557

Publikationsverlauf

Eingereicht: 13. Mai 2022

Angenommen: 06. August 2022

Artikel online veröffentlicht:
19. September 2022